A Multicenter Phase 3, Open-Label Study of Bosutinib Versus Imatinib in Adult Patients With Newly Diagnosed Chronic Phase Chronic Myelogenous Leukemia

Leukemia, Myelogenous, Chronic, Breakpoint Cluster Region-Abelson Proto-oncogene (BCR-ABL) Positive Clinical Trial

Official title:

A MULTICENTER PHASE 3 RANDOMIZED, OPEN-LABEL STUDY OF BOSUTINIB VERSUS IMATINIB IN ADULT PATIENTS WITH NEWLY DIAGNOSED CHRONIC PHASE CHRONIC MYELOGENOUS LEUKEMIA

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02130557
• Other study ID #: AV001
• Secondary ID: 2013-005101-31B1
• Status: Completed
• Phase: Phase 3
• Start date: July 15, 2014
• Est. completion date: April 17, 2020

Study information

• Verified date: April 2021
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Phase 3, 2-arm, randomized, open label trial. Patients will be randomized to receive bosutinib or imatinib for the duration of the study.

Description:

The study will be open for enrollment until the planned number of approximately 500 Philadelphia Chromosome Positive (Ph+) patients have been randomized (approximately 250 Ph+ patients in each treatment arm; a total of approximately 530 Ph+ and Ph- patients). All patients will be treated and/or followed for approximately 5 years (240 weeks) after randomization until the study has closed. Patients who discontinue study therapy early due to disease progression or intolerance to study medication will continue to be followed yearly for survival for up to approximately 5 years (240 weeks) after randomization.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 536
• Est. completion date: April 17, 2020
• Est. primary completion date: August 11, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Molecular diagnosis of CP CML of = 6 months (from initial diagnosis).

2. Adequate hepatic, renal and pancreatic function.

3. Age = 18 years.

Exclusion Criteria:

1. Any prior medical treatment for CML, including tyrosine kinase inhibitors (TKIs), with the exception of hydroxyurea and/or anagrelide treatment, which are permitted for up to 6 months prior to study entry (signature of ICF) if suitably approved for use in the subject's region.

2. Any past or current Central Nervous System (CNS) involvement, including leptomeningeal leukemia.

3. Extramedullary disease only.

4. Major surgery or radiotherapy within 14 days of randomization.

5. History of clinically significant or uncontrolled cardiac disease.

6. Known seropositivity to human immunodeficiency virus (HIV), current acute or chronic hepatitis B (hepatitis B surface-antigen positive), hepatitis C, cirrhosis or evidence of decompensated liver disease. Patients with resolved Hepatitis B can be included.

7. Recent or ongoing clinically significant GI disorder, e.g. Crohn's Disease, Ulcerative Colitis, or prior total or partial gastrectomy.

8. History of another malignancy within 5 years with the exception of basal cell carcinoma or cervical carcinoma in situ or stage 1 or 2 cancer that is considered adequately treated and currently in complete remission for at least l2 months.

9. Current, or recent (within 30 days, or 5 half-lives of investigational product) participation in other clinical trials of investigational agents and/or containing interventional procedures deemed contrary to the objectives and conduct of this trial.

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive
• Leukemia, Myelogenous, Chronic, Breakpoint Cluster Region-Abelson Proto-oncogene (BCR-ABL) Positive
• Leukemia, Myeloid
• Leukemia, Myeloid, Chronic-Phase

Intervention

Drug:
• Bosutinib
Bosutinib (Bosulif®) is an orally bioavailable, potent, multi-targeted, dual Src-Abl tyrosine kinase inhibitor (TKI) that has been approved for the treatment of adult patients with Philadelphia positive (Ph+) chronic phase (CP), accelerated phase (AP) and blast phase (BP) chronic myelogenous leukemia (CML) previously treated with other TKI inhibitor therapy.[1] This study will investigate the use of bosutinib as first-line treatment for patients with Ph+ CP CML.
• Imatinib
Imatinib mesylate (referred to in this protocol as imatinib) is an inhibitor of the BCR-ABL kinase and been the standard first-line therapy for patients with chronic-phase CML. Imatinib was granted approval by the European Commission in November 2001 and by the FDA in December 2002 for the treatment of newly diagnosed patients with CP Ph+ CML based on results from the IRIS trial. Imatinib is considered the standard of care for both first-line and later line settings, and consequently is an appropriate active comparator.

Locations

Country	Name	City	State
Australia	Eastern Clinical Research Unit, Level 2	Box Hill	Victoria
Australia	St George Hospital - Hematology Department	Kogarah	New South Wales
Belgium	UZ Ghent (University Hospital Ghent)	Ghent
Belgium	Department of Haematology at UZ Leuven (7 th Floor)	Leuven
Belgium	Hematology Department of CHU de Liège	Liège
Belgium	Hematology Department CHR Verviers	Verviers
Canada	Juravinski Cancer Centre	Hamilton	Ontario
Canada	Horizon Health Network - The Moncton Hospital	Moncton	New Brunswick
Canada	Hopital Maisonneuve-Rosemont	Montreal	Quebec
Canada	Lakeridge Health	Oshawa	Ontario
Canada	CHU de Québec - Université Laval	Quebec
Canada	Saskatoon Cancer Centre	Saskatoon	Saskatchewan
Canada	Princess Margaret Cancer Centre	Toronto	Ontario
Czechia	Fakultní Nemocnice Brno	Brno
Czechia	Fakultní Nemocnice Hradec Králové	Hradec Králové
Czechia	Fakultní nemocnice Olomouc	Olomouc
Czechia	Všeobecná fakultní Nemocnice v Praze	Prague
Denmark	Aalborg University Hospital	Aalborg
Denmark	Aarhus University Hospital	Aarhus
Denmark	Roskilde Hospital	Roskilde
Finland	Helsinki University Central Hospital	Helsinki
France	Institut Bergonié	Bordeaux
France	private Practice of Pr Philippe Rousselot	Le Chesnay
France	private Practice of Dr. Viviane Dubruille	Nantes cedex 1
France	Hôpital L'Archet 1-CHU Nice	Nice
France	Institut de Cancérologie du Gard - Hématologie Clinique	Nimes
France	Pr Mauricette Michallet Centre Hospitalier Lyon Sud	Pierre Bénite
France	INSERM CIC 1402 - CHU Poitiers	Poitiers
France	Oncologie Centre de Radiotherapie	Strasbourg	NC
France	Institut Universitaire du Cancer de Toulouse - Oncopole	Toulouse cedex 9
Germany	Uniklinikum Aachen	Aachen
Germany	Charité, CVK, Med. Klinik m.S Hämatologie und Onkologie	Berlin
Germany	Universitätsklinikum Bonn	Bonn	RP
Germany	Universitätsklinikum Freiburg, Klinik für Innere Medizin I	Freiburg
Germany	Universitätsklinikum Hamburg-Eppendorf, Onkologisches Zentrum	Hamburg
Germany	Universitätsklinikum Jena, Klinik für Innere Medizin II	Jena Lobeda-Ost
Germany	Schwerpunktpraxis für Hämatologie und Onkologie	Magdeburg
Hungary	Semmelweis Egyetem I. Belgyógyászat	Budapest
Hungary	Debreceni Egyetem Klinikai Központ, Belgyógyászati Inézet Hematológiai Tanszék	Debrecen
Hungary	Petz Aladár Megyei OktatóKórház, II. Belgyógyászati Osztály és Haematológiai Részleg	Györ
Hungary	Somogy Megyei Kaposi Mór Oktató Kórház	Kaposvár
Hungary	Szegedi Tudományegyetem, AOK, Szent-Györgyi Albert Klinikai Központ, II. sz.	Szeged
Hungary	Jász-Nagykun-Szolnok Megyei Hetényi, Géza Kórház-Rendelointézet	Szolnok
Israel	Hematology Department, Rambam Medical Centre	Haifa
Israel	Hematology Div. Davidoff Cancer Center, Rabin Medical Center	Petah-Tikva
Italy	USC Ematologia, A. O. Papa Giovanni XXIII	Bergamo
Italy	Policlinico S. Orsola - Malpighi,	Bologna
Italy	A.O. Brozu - P.O. Armando Businco	Cagliari
Italy	Azienda Ospedaliero-Universitaria "Policlinico - Vittorio Emanuele" - P.O. G. Rodolico	Catania	CT
Italy	Azienda Ospedaliero Universitaria Careggi	Firenze
Italy	IRCCS - AOU San Martino_IST, Ematologia 1	Genova
Italy	Istituto Scientifico San Raffaele	Milano
Italy	Unità di Ricerca Clinica, U.O. Ematologia Adulti	Monza
Italy	A.O.U. Policlinico Università degli Studi di Napoli "Federico II"	Napoli
Italy	Dipartimento di ematologia	Reggio Calabria
Italy	ASL Roma 2 - Ospedale Sant'Eugenio	Roma
Korea, Republic of	Hallym University Sacred Heart Hospital	Anyang-si
Korea, Republic of	Dong A University Hospital	Busan
Korea, Republic of	Keimyung University Dongsan Hospital	Daegu
Korea, Republic of	Chonbuk National University Hospital	Jeonju
Korea, Republic of	Kangbuk Samsung Hospital	Seoul
Korea, Republic of	Seoul St. Mary's Hospital of the Catholic University of Korea	Seoul
Mexico	Hospital Angeles del Pedregal (S.A. de C.V.)	Mexico City	DF
Mexico	Monterrey International Research Center	Monterrey	Nuevo LEON
Netherlands	Klinische Farrnacologie en Apotheek	Amsterdam	Noord-holland
Netherlands	VU University Medical Center	Amsterdam	Noord Holland
Norway	Haukeland University Hospital Department of Hematology	Bergen
Norway	St. Olavs Hospital	Trondheim
Poland	SPZOZ ZSM w Chorzowie Oddzial Hematologiczny	Chorzow
Poland	Klinika Hematologii i Transplantologii Uniwersyteckie Centrum Kliniczne	Gdansk	Pomorskie
Poland	Samodzielny Publiczny Szpital Kliniczny im. A Mieleckiego, SUM w Katowicach	Katowice
Poland	Szpital Uniwersytecki w Krakowie, Oddzial Kliniczny Hematologii	Kraków
Poland	Wojewódzki Szpital Specjalistyczny im M. Kopernika, Klinika Hematologii Uniwersytetu Medycznego	Lódz
Poland	SPSK, Klinika Hematoonkologii i Transplantacji Szpiku w Lublinie	Lublin
Poland	Universytet Medyczny im. Piastów Slaskich we Wroclawiu Katedra i	Wroclaw
Singapore	National University Hospital, Main Building	Singapore
Singapore	Singapore General Hospital	Singapore
Singapore	Tan Tock Seng Hospital	Singapore
Slovakia	Univerzitná Nemocnica Bratislava-Nemocnica sv. Cyrila a Metoda	Bratislava
South Africa	Department of Haematology	Cape Town	Western CAPE
South Africa	The Medical Oncology Centre of Rosebank	Johannesburg	Gauteng
South Africa	Department of Medical Oncology, University of Pretoria and Steve Biko	Pretoria	Gauteng
South Africa	Groenkloof Life hospital.	Pretoria	Gauteng
Spain	Hospital (Universitari(o)) Germans Trias i Pujol	Badalona	Barcelona
Spain	Hospital Clínic	Barcelona
Spain	Hospital Vall d'Hebron	Barcelona
Spain	Hospital Clinico San Carlos	Madrid
Spain	Hospital Ramón y Cajal	Madrid
Spain	Hospital Universitario Gregorio Marañón	Madrid
Spain	Hospital Universitario La Princesa	Madrid	Málaga
Spain	Hospital Universitario de Salamanca	Salamanca
Spain	Hospital Virgen de la Salud	Toledo
Spain	Hospital Clínico Universitario de Valencia	Valencia
Sweden	Linköping University Hospital	Linköping
Sweden	Skåne University Hospital	Lund
Sweden	Karolinska University Hospital Solna	Stockholm
Sweden	Norrlands University Hospital	Umeå
Sweden	Akademiska Hospital	Uppsala
Taiwan	Kaohsiung Medical University Chung-Ho Memorial Hospital	Kaohsiung City
Taiwan	China Medical University Hospital	Taichung city	R.o.c.
Taiwan	Chi-Mei Medical Center	Tainan City	R.o.c.
Taiwan	Mackay Memorial Hospital	Taipei City	R.o.c.
Thailand	Division of Hematology, Department of Medicine, Faculty of Medicine Siriraj Hospital	Bangkok
Thailand	King Chulalongkorn Memorial Hospital	Bangkok
Thailand	Phramongkutklao Hospital	Bangkok
Thailand	Division of Hematology, Department of Internal Medicine, Maharaj Nakorn Chiang Mai Hospital	Muang	Chiang MAI
Ukraine	MI "Cherkasy Regional Oncological Dispensary " of Cherkasy Regional Council	Cherkasy
Ukraine	Regional Clinical Hospital in Ivano-Frankivsk, Hematology Department	Ivano-Frankivsk
Ukraine	Khmelnytskyi Regional Hospital, Hematology Department	Khmelnytskyi
Ukraine	Chair of internal medicine #2.	Kyiv
Ukraine	Kyiv City Clinical Hospital #9, Hematology department #1,	Kyiv
Ukraine	State Institution "National research center for radiation medicine of NAMS of Ukraine"	Kyiv
Ukraine	State Institution "National research center for radiation medicine of NAMS of Ukraine",	Kyiv
Ukraine	transplantation department of hemotology and transplantology division within Clinical Radiology	Kyiv
Ukraine	State Institution "Institute of Blood Pathology and Transfusion Medicine NAMS of Ukraine"	Lviv
United Kingdom	Heartlands Hospital	Birmingham	WEST Midlands
United Kingdom	Department of Haematology	Cardiff
United Kingdom	St James's Institute of Oncology	Leeds	WEST Yorkshire
United Kingdom	The Hope Clinical Trials Facility	Leicester
United Kingdom	Linda McCartney Centre	Liverpool	Merseyside
United Kingdom	Catherine Lewis Centre, Hammersmith Hospital	London	Greater London
United Kingdom	Department of Clinical Haematology	Nottingham	Nottinghamshire
United Kingdom	Cancer & Haematology Centre, Churchill Hospital	Oxford	Oxfordshire
United Kingdom	Department of Haematology The Royal Hallamshire Hospital	Sheffield	South Yorkshire
United States	Pacific Cancer Medical Center, Inc.	Anaheim	California
United States	St. Joseph Mercy Hospital	Ann Arbor	Michigan
United States	St. Joseph Mercy Hospital - Inpatient Pharmacy	Ann Arbor	Michigan
United States	Emory University Hospital	Atlanta	Georgia
United States	The Emory Clinic	Atlanta	Georgia
United States	Winship Cancer Institute, Emory University	Atlanta	Georgia
United States	Rcca Md Llc	Bethesda	Maryland
United States	Saint Alphonsus Regional Medical Center	Boise	Idaho
United States	Saint Alphonsus Regional Medical Center, Cancer Care Center	Boise	Idaho
United States	St. Joseph Mercy-Brighton	Brighton	Michigan
United States	Saint Alphonsus Caldwell Cancer Care Center	Caldwell	Idaho
United States	St. Joseph Mercy-Canton	Canton	Michigan
United States	MUSC University Hospital	Charleston	South Carolina
United States	MUSC University of South Carolina, Investigational Drug Services	Charleston	South Carolina
United States	MUSC-Hollings Cancer Center	Charleston	South Carolina
United States	Chelsea Community Hospital	Chelsea	Michigan
United States	John H. Stroger, Jr. Hospital of Cook County	Chicago	Illinois
United States	University of Illinois Cancer Center	Chicago	Illinois
United States	University of Cincinnati Medical Center	Cincinnati	Ohio
United States	St. John Hospital&Medical Center	Detroit	Michigan
United States	GHS Cancer Institute	Easley	South Carolina
United States	Minnesota Oncology Hematology, PA	Edina	Minnesota
United States	San Juan Oncology Associates	Farmington	New Mexico
United States	HSHS St. Vincent Hospital	Green Bay	Wisconsin
United States	HSHS St. Vincent Hospital Regional Cancer Center at HSHS St. Mary's Hospital Medical Center	Green Bay	Wisconsin
United States	HSHS St. Vincent Hospital Regional Cancer Center at HSHS St. Vincent Hospital	Green Bay	Wisconsin
United States	GHS Cancer Institute	Greenville	South Carolina
United States	GHS Cancer Institute	Greenville	South Carolina
United States	GHS Cancer Institute	Greer	South Carolina
United States	St. John Hospital&Medical Center-Van Elslander Cancer Center	Grosse Pointe Woods	Michigan
United States	Van Elslander Cancer Center, Pharmacy	Grosse Pointe Woods	Michigan
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	John Theurer Cancer Center at Hackensack University Medical Center	Hackensack	New Jersey
United States	Kaiser Permanente Hawaii	Honolulu	Hawaii
United States	The University of Texas, MD Anderson Cancer Center	Houston	Texas
United States	Indiana Blood and Marrow Transplantation	Indianapolis	Indiana
United States	PHARMACY Department Franciscan St. Francis Health ATTN:Jill Leslie, Pharm D	Indianapolis	Indiana
United States	Cancer Center of Acadiana at Lafayette General Medical Center	Lafayette	Louisiana
United States	Lafayette General Medical Center	Lafayette	Louisiana
United States	Froedtert Hospital and the Medical College of Wisconsin	Milwaukee	Wisconsin
United States	NYU Winthrop Hospital - Oncology / Hematology department	Mineola	New York
United States	NYU Winthrop Hospital - Pharmacy Department	Mineola	New York
United States	Utah Cancer Specialists	Murray	Utah
United States	Saint Alphonsus Medical Center Nampa	Nampa	Idaho
United States	Beth Israel Medical Center	New York	New York
United States	Nebraska Methodist Hospital	Omaha	Nebraska
United States	FirstHealth Moore Regional Hospital	Pinehurst	North Carolina
United States	FirstHealth Outpatient Cancer Center	Pinehurst	North Carolina
United States	University of Rochester	Rochester	New York
United States	University of Rochester Investigational Drug Pharmacy	Rochester	New York
United States	Park Nicollet Frauenshuh Cancer center	Saint Louis Park	Minnesota
United States	Huntsman Cancer Hospital	Salt Lake City	Utah
United States	Huntsman Cancer Institute	Salt Lake City	Utah
United States	Utah Cancer Specialists	Salt Lake City	Utah
United States	Seattle Cancer Care Alliance	Seattle	Washington
United States	Virginia Mason Medical Center	Seattle	Washington
United States	GHS Cancer Institute	Seneca	South Carolina
United States	LSU Health Sciences Center-Shreveport	Shreveport	Louisiana
United States	University Health Shreveport	Shreveport	Louisiana
United States	GHS Cancer Institute	Spartanburg	South Carolina
United States	Lakeview Hospital	Stillwater	Minnesota
United States	North Mississippi Medical Center Hematology and Oncology Clinic	Tupelo	Mississippi
United States	UC Health Physicians Office South,	West Chester	Ohio
United States	University of Massachusetts Memorial Medical Center	Worcester	Massachusetts
United States	University of Massachusetts Memorial Medical Center, ONC/Research Pharmacy	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Canada,  Czechia,  Denmark,  Finland,  France,  Germany,  Hungary,  Israel,  Italy,  Korea, Republic of,  Mexico,  Netherlands,  Norway,  Poland,  Singapore,  Slovakia,  South Africa,  Spain,  Sweden,  Taiwan,  Thailand,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Summary of Trough Plasma Concentration by Complete Cytogenetic Response (CCyR) of Bosutinib	CCyR was based on the prevalence of Ph+ metaphases among cells in metaphase on a BM aspirate. CCyR was achieved when there was 0% Ph+ metaphases among cells in a BM sample when at least 20 metaphases from a BM sample were analyzed, or MMR if no BM was available. Trough plasma concentration of participants who had CCyR are presented in this outcome measure.	Pre-dose on Days 28, 56 and 84
Other	Summary of Trough Plasma Concentration by Major Molecular Response (MMR) of Bosutinib	MMR was defined as a ratio of BCR-ABL/ABL <=0.1% on the international scale (>=3 log reduction from standardized baseline in ratio of BCR-ABL to ABL transcripts) by quantitative RT-qPCR. Trough plasma concentration of participants who had MMR are presented in this outcome measure.	Pre-dose on Days 28, 56 and 84
Other	Summary of Trough Plasma Concentration by Presence of Grade 1 or Higher Adverse Events (AEs) of Bosutinib	An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. AE was assessed according to maximum severity grading based on National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Grade 1= mild; Grade 2= moderate; within normal limits, Grade 3= severe or medically significant but not immediately life-threatening; Grade 4= life-threatening or disabling; urgent intervention indicated; Grade 5= death. Trough plasma concentration of participants who had grade 1 or higher AE are presented in this outcome measure. Data of plasma concentration is reported separately for each preferred term of AE.	Pre-dose on Days 28, 56 and 84
Other	Summary of Trough Plasma Concentration by Presence of Grade 3 or Higher Adverse Events (AEs) of Bosutinib	An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. AE was assessed according to maximum severity grading based on NCI CTCAE version 4.0. Grade 1= mild; Grade 2= moderate; within normal limits, Grade 3= severe or medically significant but not immediately life-threatening; Grade 4= life-threatening or disabling; urgent intervention indicated; Grade 5= death. Trough plasma concentration of participants who had grade 3 or higher AE are presented in this outcome measure. Data of plasma concentration is reported separately for each preferred term of AE.	Pre-dose on Days 28, 56 and 84
Other	Number of Participants With Vital Signs Abnormalities	Criteria for vital signs abnormalities: systolic blood pressure <80 millimeter of mercury (mmHg), >210 mmHg; diastolic blood pressure <40 mmHg, >130 mmHg; heart rate <40 beats per minute (bpm), >150 bpm; temperature <32 degree celsius, >40 degree celsius; weight >=10% increase from baseline, >=10% decrease from baseline. The number of participants with any vital sign abnormalities during On-treatment period are reported. On-Treatment was defined as values collected after the date of the first dose of test article until the last date of test article +28 days.	Baseline up to end of treatment (up to Month 60)
Other	Number of Participants With Laboratory Test Abnormalities Based on National Cancer Institute Common Terminology Criteria for AEs (NCI CTCAE) Version 4.03	Laboratory parameters included hematological (haemoglobin, lymphocytes [absolute], neutrophils [absolute], platelets and leukocytes) and biochemistry (albumin, alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, amylase, bilirubin, creatinine kinase, calcium, creatinine, glucose, potassium, lipase, magnesium, phosphate, sodium, urate) parameters. Abnormalities in laboratory tests were graded by NCI CTCAE version 4.03 as Grade 1= mild; Grade 2= moderate; Grade 3= severe and Grade 4= life-threatening or disabling. The number of participants with laboratory test abnormalities were reported.	Baseline up to end of treatment (up to Month 60)
Other	Number of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities	Criteria for ECG abnormalities included heart rate: increase of >15 bpm from baseline value and >=120 bpm, decrease of >15 bpm from baseline value and <=45 bpm; PR interval: change of >=20 msec from baseline value and >=220 milliseconds (msec); QRS interval >=120 msec; QTcB interval >500 msec, increase of >60 msec from baseline; >450 msec (Men) or >470 msec (Women). QT interval using Fridericia's correction (QTcF) >500 msec, increase of >60 msec from baseline, >450 msec (Men) or >470 msec (Women). The number of participants with ECG abnormalities during On-treatment period are reported. On-Treatment was defined as values collected after the date of the first dose of test article up until the last date of test article +28 days.	Baseline up to end of treatment (up to Month 60)
Other	Number of Participants With Adverse Events (AEs) Leading to Study Drug Discontinuation	An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship.	Baseline up to end of treatment (up to Month 60)
Other	Number of Participants With Treatment-Emergent Adverse Events by National Cancer Institute Common Terminology Criteria for AEs (NCI CTCAE) (Version 4.0)	An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. AE was assessed according to severity grading based on NCI CTCAE version 4.0. Grade 1 =mild; Grade 2 =moderate; Grade 3 =severe or medically significant but not immediately life-threatening, hospitalization or prolongation of hospitalization indicated; Grade 4 =life-threatening or disabling, urgent intervention indicated; Grade 5 =death. Treatment-emergent events were events between first dose of study drug and up to 60 months that were absent before treatment that worsened relative to pretreatment state. If the same participant in a given treatment had more than 1 adverse event, only the maximum CTCAE was reported.	Baseline up to end of treatment (up to Month 60)
Primary	Percentage of Participants With Major Molecular Response (MMR) at Month 12	MMR was defined as a ratio of breakpoint cluster region to abelson (BCR-ABL/ABL) less than or equal to (<=) 0.1 percent (%) on the international scale (IS) (greater than or equal to [>=] 3 log reduction from standardized baseline in ratio of BCR-ABL to ABL transcripts [>=3000 ABL required]) by quantitative reverse transcriptase polymerase chain reaction (RT-qPCR). The percentage of participants with MMR at Month 12 are reported.	Month 12
Secondary	Percentage of Participants With Major Molecular Response (MMR) Up to Month 18	MMR was defined as a ratio of BCR-ABL/ABL <=0.1% on the international scale (>=3 log reduction from standardized baseline in ratio of BCR-ABL to ABL transcripts [>=3000 ABL required]) by quantitative RT-qPCR. The percentage of participants with MMR for up to Month 18 are reported.	Up to Month 18
Secondary	Kaplan-Meier Estimate of Probability of Retaining Major Molecular Response (MMR) at Month 48	The Kaplan-Meier curve was generated based on the first date of MMR until the date of the confirmed loss of MMR or censoring, objectively documented, for responders only. Confirmed loss of MMR was BCR-ABL/ABL IS ratio >0.1% in association with a >=5-fold increase in BCR-ABL/ABL IS ratio from the lowest value achieved up to that time-point confirmed by a second assessment at least 28 days later. Treatment discontinuation due to suboptimal response/treatment failure, progressive disease (PD) or death due to PD within 28 days of last dose were considered confirmed loss of MMR. PD was defined as disease progression to accelerated phase (AP) or blast phase (BP) CML.	Month 48
Secondary	Percentage of Participants With Complete Cytogenetic Response (CCyR) Up to Month 12	Complete Cytogenetic Response (CCyR) was based on the prevalence of Ph+ metaphases among cells in metaphase on a bone marrow (BM) aspirate. CCyR was achieved when there was 0% Ph+ metaphases among cells in a BM sample when at least 20 metaphases from a BM sample were analyzed, or MMR if no BM was available. The percentage of participants with CCyR for up to Month 12 are reported.	Up to Month 12
Secondary	Kaplan-Meier Estimate of Probability of Retaining Complete Cytogenetic Response (CCyR) at Month 48	The Kaplan-Meier curve was generated based on the first date of CCyR until the date of the confirmed loss of CCyR or censoring, objectively documented, for responders only. Confirmed loss of CCyR was the presence of at least one Ph+ metaphase confirmed by a second assessment at least 28 days later. Treatment discontinuation due to suboptimal response/treatment failure, PD or death due to PD within 28 days of last dose were considered confirmed loss of CCyR. PD was defined as disease progression to AP or BP CML.	Month 48
Secondary	Cumulative Incidence of Event Free Survival (EFS) Events	EFS was defined as time from randomization to death due to any cause, transformation to AP or BP at any time, confirmed loss of complete hematologic response (CHR), confirmed loss of CCyR or censoring. Loss of CHR was defined as a hematologic assessment of non-CHR (chronic phase, AP, or BP) confirmed by 2 assessments at least 4 weeks apart. Loss of CHR was defined as appearance of any of the following: WBC count that rises to >20.0*10^9/L, platelet count rises to >=600*10^9/L, appearance of palpable spleen or other extramedullary involvement proven by biopsy, appearance of 5% myelocytes in peripheral blood, appearance of blasts or promyelocytes in peripheral blood. Loss of CCyR was defined as at least 1 Ph+ metaphase from analysis of <100 metaphases confirmed by follow up cytogenetic analysis after 1 month. Cumulative incidence of EFS was defined as percentage of participants with EFS event at Month 60 and was adjusted for competing risk of treatment discontinuation without event.	Up to Month 60
Secondary	Overall Survival (OS) Rate	OS was defined as the time (in months) from randomization to the occurrence of death due to any cause or censoring. Kaplan-meier analysis was used for determination of OS. Percentage of participants who were alive were estimated in this outcome measure.	Up to Month 60